Optimizing anesthesia to prevent postoperative cognitive and functional decline in older adults

优化麻醉以防止老年人术后认知和功能下降

• 批准号: 10681435
• 负责人: Katie Jo Schenning
• 金额: $ 24.3万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10681435
• 关键词: Active Learning; Affect; Age; Age Years; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; American; Amyloid beta-Protein; Anesthesia procedures; Anesthesiology; Anesthetics; Anti-Inflammatory Agents; Award; Biological Markers; Blood; Clinical; Clinical Trials; Consensus; Data; Dedications; Delirium; Dementia; Development Plans; Disease; Double-Blind Method; Elderly; Evidence based practice; Exposure to; Friends; Functional disorder; General Anesthesia; General anesthetic drugs; Geriatrics; Goals; Health; Health Care Costs; Human; Impaired cognition; In Vitro; Incidence; Inflammatory; Inhalation; Inhalation Anesthesia; Inpatients; Institution; Intervention Trial; Interview; Intravenous; Intravenous Anesthesia; Investigation; Knowledge; Lead; Leadership; Length of Stay; Literature; Maintenance; Medicine; Mentors; Mentorship; Meta-Analysis; Modality; Neurocognitive Deficit; Neuronal Injury; Operative Surgical Procedures; Outcome; Outcomes Research; Participant; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Perioperative; Perioperative Care; Personal Satisfaction; Pharmaceutical Preparations; Physicians; Plasma; Population; Positioning Attribute; Postoperative Period; Production; Property; Propofol; Public Health; Randomized; Research; Research Proposals; Risk; Risk Factors; Role; Scientist; Severities; Surgical complication; Techniques; Testing; Training; Translating; Venous blood sampling; Woman; abeta oligomer; age related; blood-based biomarker; career; career development; clinical practice; cost; cost effective; disability; effective intervention; experience; functional decline; functional disability; functional improvement; functional status; high risk; improved; in vivo; medical specialties; meetings; men; modifiable risk; mortality; multidisciplinary; neurocognitive test; neuroinflammation; neuron apoptosis; neurotoxic; neurotoxicity; older patient; operation; post-operative cognitive dysfunction; postoperative delirium; preclinical study; prevent; secondary outcome; skills training; tau-1

ABSTRACT: Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are the most common surgical complications in older adults and are associated with increased hospital length of stay, functional disability, mortality, and risk of Alzheimer’s. In the U.S., anesthesia is maintained with inhalational agents (GAS) in up to 90% of operations; however, maintenance with intravenous agents (IV) is an alternative technique with potential advantages. There is a significant gap in knowledge regarding whether IV vs. GAS can decrease the risk of deleterious postoperative outcomes in older surgical patients. This is a critical public health problem considering over half of older Americans will undergo surgery during their lives, and the surgical population is aging faster than the U.S. population. Considering both GAS and IV are readily available, effective, safe, and cost-effective, switching from one to the other would be a simple clinical practice change. Career Development Plan: The candidate is dedicated to an academic career in perioperative aging research and will focus on four objectives. (1) Training to become a clinical trialist and lead multidisciplinary teams conducting trials in older adults. Develop expertise in incorporating (2) geriatric medicine principles and (3) biomarker investigations into perioperative intervention trials in older adults. (4) Enhance leadership training to be an effective leader in geriatric anesthesiology research and effect change in clinical practice. Objectives will be met by formal coursework, meetings, seminars, mentoring, skills training, and experiential learning with a dedicated mentorship team in a supportive academic department and institution. Completion will enable the candidate to achieve the goal of becoming an independent physician-scientist and a leader in geriatric anesthesia research focused on preventing neurocognitive and functional decline in older surgical patients. Research Proposal: The specific aims are to determine the effects of IV vs. GAS on (1) incidence of POD and POCD in older adults; (2) incidence of postoperative functional decline and patient-reported outcomes (PROs) in older adults; and (3) levels of phosphorylated tau 181 (p-tau181) and other blood biomarkers in older adults. Hypotheses: There is a decreased incidence of POD, POCD, and functional decline following surgery and general anesthesia with IV vs. GAS. Next, compared to GAS, IV will improve PROs and decrease neuroinflammatory and Alzheimer’s blood-based biomarkers. Specifically, the postoperative increase in blood p-tau181 is greater in GAS than IV and is associated with POD and POCD. Approach: This single-center, 1:1 randomized, double-blind clinical trial will compare GAS vs. IV on POD, POCD, functional status, and PROs in men and women ≥ 75 years of age undergoing elective, inpatient, non-cardiac surgery. Results will provide evidence to aid the choice of general anesthetic (IV vs. GAS) to optimize outcomes in geriatric surgical patients. This aligns with the NIA’s strategic goal to develop effective interventions to maintain health, well-being, and function, and reduce the burden of age-related disorders and disabilities.

摘要：背景：在美国，术后谵妄 (POD) 和术后认知功能障碍 (POCD) 是老年人最常见的手术并发症，与住院时间延长、功能障碍、死亡率和阿尔茨海默病风险相关。高达 90% 的手术采用吸入剂 (GAS) 维持；然而，静脉注射剂 (IV) 维持是一种具有潜在优势的替代技术，关于 IV 与 GAS 之间的知识存在显着差距。考虑到超过一半的美国老年人在其一生中会接受手术，并且考虑到 GAS 和 IV，手术人群的老龄化速度比美国人口更快，这是一个重要的公共卫生问题。容易获得、有效、安全且具有成本效益，从一种转换到另一种将是一个简单的临床实践改变。 职业发展计划：候选人致力于围手术期衰老研究的学术生涯，并将重点关注四个目标。 (1) 临床试验师培训领导多学科团队开展老年人试验。发展将 (2) 老年医学原则和 (3) 生物标志物研究纳入老年人围手术期干预试验的专业知识。 (4) 加强领导力培训，成为老年麻醉学研究的有效领导者。目标将通过在支持性学术部门和机构的专门指导团队的正式课程、会议、研讨会、指导、技能培训和体验式学习来实现。目标是成为一名独立的医师科学家和老年麻醉研究的领导者，重点是预防老年手术患者的神经认知和功能下降。 研究建议：具体目标是确定 IV 与 GAS 对 (1) 发生率的影响。老年人的 POD 和 POCD；(2) 老年人术后功能下降的发生率和患者报告的结果 (PRO)；(3) 磷酸化 tau 181 (p-tau181) 和假设：与 GAS 相比，IV 会降低手术和全身麻醉后 POD、POCD 和功能下降的发生率。具体而言，GAS 中的术后血液 p-tau181 升高程度高于 IV，并且与 POD 和 POCD 相关。 方法：这项单中心、1:1 随机、双盲临床试验将进行。比较 75 岁以上接受择期住院非心脏手术的男性和女性中 GAS 与 IV 的 POD、POCD、功能状态和 PROs，结果将为帮助选择全身麻醉（IV 与 GAS）提供证据。 ）以优化老年外科患者的治疗效果，这符合 NIA 的战略目标，即制定有效的干预措施以维持健康、福祉和功能，并减轻与年龄相关的疾病和残疾的负担。